TY - JOUR
T1 - A Randomized Trial to Assess Safety and Immunogenicity of Alternative Formulations of a Quadrivalent Meningococcal (A, C, Y, and W-135) Tetanus Protein Conjugate Vaccine in Toddlers
AU - McVernon, Jodie
AU - Nolan, Terry
AU - Richmond, Peter
AU - Reynolds, Graham
AU - Nissen, Michael
AU - Lambert, Stephen B.
AU - Marshall, Helen
AU - Papa, Thomas
AU - Rehm, Christine
PY - 2012/1
Y1 - 2012/1
N2 - Background: Neisseria meningitidis is a leading cause of meningitis and septicemia globally. Recent shifts in serogroup dominance in some settings highlight the desirability of polysaccharide-conjugate vaccines with broader meningococcal coverage than serogroup C vaccines in widespread use. Methods: We assessed the safety and immunogenicity of a single dose of meningococcal quadrivalent (A, C, W-135, Y) tetanus conjugate vaccine (TetraMen-T), administered at 1 year of age. A total of 378 children were randomized to 1 of 6 groups-5 received alternative formulations of TetraMen-T, the sixth licensed adjuvanted serogroup C conjugate vaccine (Neisvac-C). Solicited adverse event reports were collected from day 0 to 7 after vaccination and unsolicited and serious adverse event reports throughout study participation. Immunogenicity was assessed by serum bactericidal assays containing either a human (hSBA) or baby rabbit (rSBA) complement source before and 1 month after immunization. Results: All vaccine formulations were safe and well tolerated. Using the various measures of immunogenicity, no consistent relationships were observed between the dose of either polysaccharide or carrier and serogroup-specific response for any one antigen. The highest-dose vaccine provided optimal coverage for all 4 serogroups, with the percentage of recipients achieving hSBA titers ≥8 against each as follows: A, 92%; C, 96%; W-135, 71%; Y, 82% (corresponding proportions with rSBAs titers >8 all exceeded 90%). The investigational vaccines were less immunogenic against the serogroup C capsular polysaccharide than the licensed comparator. Conclusions: Studies are ongoing that will help to identify optimal scheduling of quadrivalent meningococcal conjugate vaccines, to facilitate their inclusion into national immunization programs seeking extended serogroup coverage against meningococci.
AB - Background: Neisseria meningitidis is a leading cause of meningitis and septicemia globally. Recent shifts in serogroup dominance in some settings highlight the desirability of polysaccharide-conjugate vaccines with broader meningococcal coverage than serogroup C vaccines in widespread use. Methods: We assessed the safety and immunogenicity of a single dose of meningococcal quadrivalent (A, C, W-135, Y) tetanus conjugate vaccine (TetraMen-T), administered at 1 year of age. A total of 378 children were randomized to 1 of 6 groups-5 received alternative formulations of TetraMen-T, the sixth licensed adjuvanted serogroup C conjugate vaccine (Neisvac-C). Solicited adverse event reports were collected from day 0 to 7 after vaccination and unsolicited and serious adverse event reports throughout study participation. Immunogenicity was assessed by serum bactericidal assays containing either a human (hSBA) or baby rabbit (rSBA) complement source before and 1 month after immunization. Results: All vaccine formulations were safe and well tolerated. Using the various measures of immunogenicity, no consistent relationships were observed between the dose of either polysaccharide or carrier and serogroup-specific response for any one antigen. The highest-dose vaccine provided optimal coverage for all 4 serogroups, with the percentage of recipients achieving hSBA titers ≥8 against each as follows: A, 92%; C, 96%; W-135, 71%; Y, 82% (corresponding proportions with rSBAs titers >8 all exceeded 90%). The investigational vaccines were less immunogenic against the serogroup C capsular polysaccharide than the licensed comparator. Conclusions: Studies are ongoing that will help to identify optimal scheduling of quadrivalent meningococcal conjugate vaccines, to facilitate their inclusion into national immunization programs seeking extended serogroup coverage against meningococci.
KW - Infant
KW - Meningococcal
KW - Randomized controlled trial
KW - Tetravalent meningococcal vaccine
KW - Vaccines
UR - http://www.scopus.com/inward/record.url?scp=84855465317&partnerID=8YFLogxK
U2 - 10.1097/INF.0b013e31823e1e34
DO - 10.1097/INF.0b013e31823e1e34
M3 - Article
SN - 0891-3668
VL - 31
SP - e15-e23
JO - Pediatric Infectious Disease Journal
JF - Pediatric Infectious Disease Journal
IS - 1
ER -